Optimization of the Ugi reaction using parallel synthesis and automated liquid handling Jean-Claude Bradley Sept 23, 2008 Mettler-Toledo Webinar E-Learning Coordinator College of Arts and Sciences Associate Professor of Chemistry Drexel University

Open and Closed Science Traditional Lab Notebook (unpublished) Traditional Journal Article Open Access Journal Article Open Notebook Science (full transparency) CLOSED OPEN Traditional Paper Textbook F2F lectures Lectures Notes public Assigned problems public Archived Lectures Public and free online textbooks RESEARCH TEACHING

Motivations for ONS Faster Science Better Science

Faster Science

Better Science

UsefulChem Project: Open Primary Research in Drug Design using Web2.0 tools Docking Synthesis Testing Rajarshi Guha Indiana U JC Bradley Drexel U Phil Rosenthal UCSF (malaria) Dan Zaharevitz NCI (tumors) Tsu-Soo Tan Nanyang Inst.

BLOG WIKI Mailing List GoogleDocs Architecture: Distributed, Interlinked and Redundant ChemSpider CDD FriendFeed Nature Precedings JoVE

Where’s the Beef?

Link to Lab Notebook Page in Wiki

Link to Molecules

Link to Docking Procedure (Rajarshi Guha)

Link to Docking Results: Lists of SMILES in GoogleDocs (Rajarshi Guha)

Link to Raw Data with JSpecView (data in JCAMP-DX format) (by Robert Lancashire)

Conclusion is Fully Supported

Comparing Experiments Ugi Master Table

Concentration (0.4, 0.2, 0.07 M) Solvent (methanol, ethanol, acetonitrile, THF) Excess of some reagents (1.2 eq.) Reaction to Optimize

Concentration (0.4, 0.2, 0.07 M)

Solvent (methanol, ethanol, acetonitrile, THF)

Excess of some reagents (1.2 eq.)

Mettler-Toledo MiniBlock System

Mettler-Toledo MiniMapper

XML reports from MiniMapper robot

GoogleDoc to program and report

Paper written on Wiki

References to papers, blog posts, lab notebook pages, raw data

Paper on Journal of Visualized Experiments (JoVE)

Pre-print on Nature Precedings

Best Yield: 66% 0.4 M methanol 1.2 eq imine But… what are the trends?

At 0.2 Molar

At 0.2 Molar – complex solvent and reagent excess effects

Methanol 0.4M xs of imine best

Conclusions Parallel synthesis can be useful for finding a robust area in the reaction space Use methanol at 0.4 M – below 0.2 M precipitous decline in yield Effect of excess of some reagents not clear Open Notebook Science can be used effectively to communicate details from papers

Parallel synthesis can be useful for finding a robust area in the reaction space

Use methanol at 0.4 M – below 0.2 M precipitous decline in yield

Effect of excess of some reagents not clear

Open Notebook Science can be used effectively to communicate details from papers

Acknowledgements Khalid Mirza (Drexel) Kevin Owens (Drexel) Tom Osborne (Mettler-Toledo) Antony Williams (ChemSpider) Andrew Lang (Oral Roberts U.)

Khalid Mirza (Drexel)

Kevin Owens (Drexel)

Tom Osborne (Mettler-Toledo)

Antony Williams (ChemSpider)

Andrew Lang (Oral Roberts U.)